Researchers discover innovative new treatment approach for multiple myeloma

Through a collaborative study, researchers from the University of Arizona and the University of Southern California Comprehensive Cancer Centers showed that combining several cancer therapies created an effective immune response for patients experiencing relapse or resistance of multiple myeloma, a form of blood cancer. 

Although several new drugs have been FDA approved to treat multiple myeloma over the last decade, some patients are resistant to these therapies.

In their study, the researchers used Pelareorep or PELA, which is a viral agent called an oncolytic virus that selectively kills cancer cells, with standard regimen of bortezomib and dexamethasone. This is a safe and well-tolerated therapy for patients with relapsed or refractory multiple myeloma.

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The findings of their collaborative study were recently published in Clinical Cancer Research. The team conducted a Phase Ib clinical trial where they showed that combining PELA with bortezomib and dexamethasone causes an immune response in patients that increases specific types of immune cells called T-cells and natural killer cells in the bone marrow that help to kill the cancerous multiple myeloma cells.

“We hope that our approach will ultimately offer a safe and effective new option to improve outcomes for multiple myeloma patients who do not benefit sufficiently from conventional treatment regimens,” said first author Steffan T. Nawrocki, PhD, professor at the University of Arizona College of Medicine – Tucson in the Department of Medicine and a UArizona Cancer Center member.

Multiple myeloma is the second most common blood cancer, or hematologic malignancy, in the United States with more than 30,000 new cases diagnosed each year. In multiple myeloma, groups of fast-growing plasma cells form tumors in the soft tissue or bone that lead to progressive bone marrow failure, fractures and a vulnerability to infections.

Although newer treatments have improved survival, multiple myeloma remains incurable, and most patients become resistant to available therapies and eventually relapse. According to Nawrocki, relapse in multiple myeloma is complex and is triggered by several different immunological issues. 

“The ability of multiple myeloma cells to escape the immune system is one factor underlying relapse that has gained increasing attention over the last several years,” Nawrocki said. “The current study showed that adding PELA, to the standard bortezomib-Dex regimen leads to immune reprogramming. This may contribute to the sensitivity we observed in patients who had previously relapsed from bortezemib-Dex and other proteasome inhibitor-based regimens. We view this as an important validation of our preclinical research in this area.”

The researchers have already begun a follow up clinical trial that adds pembroluzimab (KEYTRUDA) to the PELA, dexamethasone and bortezomib combination.

Kevin R. Kelly, MD, PhD, associate professor of Clinical Medicine in the Keck School of Medicine of the University of Southern California and Nawrocki have been collaborating on multiple myeloma treatments for more than 15 years and previously worked together at the University of Texas Health Science Center’s Institute for Drug Development. 

“Although our careers have taken us to different locations since then, our collaboration has continued and we have developed multiple clinical trials together in addition to co-authoring 28 publications and counting,” Nawrocki said. “Great collaborators often become some of your best friends, which makes working together a lot of fun. That has certainly been the case with our collaboration, and I am excited to see what we will do next.”

UArizona Cancer Center member Jennifer Carew, PhD, a professor in the University of Arizona College of Medicine – Tucson in the Department of Medicine and Clinical Translational Sciences, and the director of the Investigator Initiated Clinical Trials and Translational Research, also contributed to this publication.